DESCRIPTION (Applicant's Description): AML is the most common adult-onset leukemia and the most rapidly fatal, yet the etiology of this devastating disease remains largely unknown. Ionizing radiation, such as from medical x-rays, has been shown to cause AML and dose- response has been defined in heavily exposed populations, although susceptibility has remained elusive. Studies of AML after relatively low dose exposures have been few and inconsistent. We have exciting new findings which suggest that the association with relatively low radiographic exposure is specific to AML subtypes M4 and M5. Both types are also associated with cytogenetic abnormalities in the 11q23 region. 11q23 is the location of the AT gene which appears to predispose carriers to the development of various cancers when exposed to radiation. We propose to confirm the subtype-specific association with radiography in an independent study of newly diagnosed cases and to investigate whether the association may relate to a higher than expected prevalence of ATM carrier status in M4/M5 patients who appear to have radiogenic AML. The proposed study will include 310 Los Angeles County adult-onset AML cases, diagnosed from 1999 through 2003. Cases will be neighborhood-matched to controls by birth year, race, and gender. Proxies will be used for cases unavailable for interview. Dosimetry models developed for our current study will be used to assign exposure from diagnostic x-rays. ATM heterozygosity rates will be compared between groups defined by level of exposure to medical radiation and by FAB subtype. Smoking and other potential risk factors will also be investigated. FAB subtype-specific analyses appear essential to further elucidate the etiology of AML. Identification of genetic susceptibility to particular exposures (e.g., ATM and ionizing radiation) would enable the identification of potentially preventable cases of AML.